LOCAL researchers working with an international consortium have made a breakthrough in tuberculosis (TB) diagnostics after identifying drug-resistant strains that had previously gone undetected by conventional tests.
The findings, published in the journal Nature Communications, show that targeted next-generation sequencing (tNGS) can detect forms of drug-resistant TB that routine diagnostic methods often miss.
Researchers said the discovery reveals an underestimated burden of multidrug-resistant tuberculosis (MDR-TB) in southern Africa and could improve treatment for patients.
The study assessed the use of targeted next-generation sequencing as part of routine TB care in the country, which has a high burden of MDR-TB.
The method analyses the genetic characteristics of TB bacteria directly from patient samples, providing more detailed information on drug resistance than standard diagnostic tests.
Researchers found that a form of rifampicin-resistant TB linked to the rpoB I491F mutation is frequently missed by routine diagnostic tests.
This can result in patients being classified incorrectly and receiving treatment that may not be effective.
Project coordinator Professor Stefan Niemann, Director of the Infections Programme Area at the Borstel Research Center, Leibniz Lung Center and Deputy Coordinator of the Tuberculosis Research Area at the German Centre for Infection Research (DZIF), said accurate resistance testing was essential for successful TB treatment.
“Our results show that many patients who were initially classified as having lower levels of resistance actually harboured multidrug-resistant strains that were not detected by conventional diagnostic methods,” he said.
Between June 2021 and December 2024, researchers analysed 234 patient samples from people with suspected drug-resistant TB or treatment failure.
Using targeted next-generation sequencing, they identified rifampicin resistance in 159 TB strains. Of these, 64 per cent carried the rpoB I491F mutation, which is known to be poorly detected by several widely used diagnostic tests.
The study also found high levels of resistance to bedaquiline, one of the key medicines used to treat multidrug-resistant TB.
Researchers detected genetic markers linked to bedaquiline resistance in 55 per cent of rifampicin-resistant strains and in 85 per cent of strains carrying the rpoB I491F mutation.
Debrah Vambe of the Baylor College of Medicine Children’s Foundation Eswatini, the study’s first author and principal investigator in the country, said the findings suggested that many patients could be receiving treatment that included medicines to which their TB strain was already resistant.
The introduction of targeted next-generation sequencing also had an immediate effect on patient care.
The sequencing results led to changes in treatment for 53 per cent of patients whose clinical information was available.
Despite the complex resistance patterns, treatment was successful in 88 per cent of those patients.
Researchers said the findings raised important questions about current approaches to diagnosing and classifying drug-resistant TB.
They noted that routine diagnostic tests may fail to identify rifampicin resistance linked to the rpoB I491F mutation, increasing the risk of incorrect treatment.
They also said the frequent occurrence of both rifampicin and bedaquiline resistance could reduce the effectiveness of standard treatment regimens such as BPaLM in areas where these strains are common.
The research team said wider use of sequencing-based diagnostics could improve the detection of drug resistance, reduce treatment failure and help limit the spread of resistant TB strains.
Questions were sent to Ministry of Health Communications Officer Nsindiso Tsabedze but there was no response at the time of going to print.
He had been asked what steps the ministry was taking to strengthen TB diagnostic services and ensure patients with drug-resistant TB receive the correct treatment, given the findings of the study.
The study was conducted through a collaboration involving the Baylor College of Medicine Children’s Foundation Eswatini, the Global TB Program at Baylor College of Medicine in the United States, the National Tuberculosis Reference Laboratory, Eswatini Health Laboratory Services, the Ministry of Health, the National TB Control Programme, the Research Center Borstel, Leibniz Lung Center, the German Centre for Infection Research and other partner institutions from Eswatini, Europe and the United States.
